Attenuated Semliki Forest virus for cancer treatment in dogs : safety assessment in two laboratory Beagles

Background: Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of similar to 2 x 10(5) plaque forming units of parental A7(74) strain. Results: VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions: Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.Peer reviewe

Long-term subjective results and radiologic prognosis of a distal radius fracture in working-aged patients : a prognostic cohort study of 201 patients

Objective: To investigate long-term outcomes associated with distal radius fracture (DRF) in working-aged patients. The authors hypothesized that the majority of patients experience no permanent loss of function when measured with patient-rated wrist evaluation (PRWE). Methods: This was a retrospective cohort study of patients with a DRF aged between 18 and 65 years. The primary outcome measure was PRWE score at a minimum of 4 years after DRF. Secondary outcome measures were pain catastrophizing scale (PCS) and radiographic measurements. Results: Of 201 patients included, 179 were primarily treated non-operatively with a 5-week cast treatment and 22 were primarily operated. The mean follow-up duration was 5 years. The mean PRWE score was 10.9 (95% confidence interval 8.4, 13.4) and median PRWE was 3.5 (interquartile range, 0.0–13.0). There was minor correlation between PCS and PRWE score (correlation coefficient [CC] 0.3), and between PRWE score and dorsal angulation of the fracture measured after closed reduction (CC 0.2) and in one-week follow-up radiographs (CC 0.2). Conclusions: Working-aged patients seem to gain nearly normal wrist function after DRF in longer follow-up. Pain catastrophizing appears to correlate with long-term treatment outcome.publishedVersionPeer reviewe

Cardiorespiratory fitness is associated with sickness absence and work ability

BACKGROUND: Physical activity may sustain the physical aspect of work ability despite health problems such as musculoskeletal disorders and anxiety, which are the most prevalent work-related health problem in Europe. AIMS: To evaluate the association of Finnish municipal workers' accelerometer-measured physical activity, sedentary behaviour, and cardiorespiratory and muscular fitness with their sickness absence levels, perceived work ability and health-related quality of life. METHODS: In connection with a randomized controlled trial recruiting 185 municipal workers, the authors performed baseline data analysis utilizing quantile regression to examine relationships between the outcome variables (all-cause sickness absence for 6 months, perceived work ability and health-related quality of life) and cardiorespiratory fitness, muscular fitness, and physical activity, and sedentary behaviour. All results were adjusted for age, sex and education level. RESULTS: The median duration of all-cause sickness absence over the preceding 6 months was lowest among participants with high cardiorespiratory fitness relative to the lowest tertile (2.0 versus 6.0 days; P < 0.05), and the highest perceived work ability was found among those with high or moderate cardiorespiratory fitness as compared to the lowest tertile (8.0 versus 7.0; P < 0.001). Moderate-to-vigorous physical activity correlated positively with the physical component of health-related quality of life (P < 0.01) and with a high cardiorespiratory-fitness level (P < 0.05). CONCLUSIONS: High cardiorespiratory fitness was associated with decreased all-cause sickness absence days and improved work ability among municipal workers.publishedVersionPeer reviewe

Personalised eHealth intervention to increase physical activity and reduce sedentary behaviour in rehabilitation after cardiac operations: Study protocol for the PACO randomised controlled trial (NCT03470246)

Introduction: Personalized intervention to increase physical Activity and reduce sedentary behaviour in rehabilitation after Cardiac Operations (PACO) is a smartphone-based and accelerometer-based eHealth intervention to increase physical activity (PA) and reduce sedentary behaviour (SB) among patients recovering from cardiac surgery.Design: Prospective randomised controlled trial.Methods and analysis: The present protocol describes a randomised controlled clinical trial to be conducted in the Heart Centres of Kuopio and Turku university hospitals. The trial comprises 540 patients scheduled for elective coronary artery bypass grafting, aortic valve replacement or mitral valve repair. The patients will be randomised into two groups. The control group will receive standard postsurgical rehabilitation guidance. The eHealth intervention group will be given the same guidance together with personalised PA guidance during 90 days after discharge. These patients will receive personalised daily goals to increase PA and reduce SB via the ExSedapplication. Triaxial accelerometers will be exploited to record patients’ daily accumulated PA and SB, and transmit them to the application. Using the accelerometer data, the application will provide online guidance to the patients and feedback of accomplishing their activity goals. The data will also be transmitted to the cloud, where a physiotherapist can monitor individual activity profiles and customise the subsequent PA and SB goals online. The postoperative improvement in patients’ step count, PA, exercise capacity, quality of sleep, laboratory markers, transthoracic echocardiography (TTE) parameters and quality of life, and reduction in SB and incidence of major cardiac events are investigated as outcomes.Conclusions: The PACO intervention aims to build a personalised eHealth tool for the online tutoring of cardiac surgery patients.</p

Cross-species amplification of 41 microsatellites in European cyprinids: A tool for evolutionary, population genetics and hybridization studies

<p>Abstract</p> <p>Background</p> <p>Cyprinids display the most abundant and widespread species among the European freshwater Teleostei and are known to hybridize quite commonly. Nevertheless, a limited number of markers for conducting comparative differentiation, evolutionary and hybridization dynamics studies are available to date.</p> <p>Findings</p> <p>Five multiplex PCR sets were optimized in order to assay 41 cyprinid-specific polymorphic microsatellite loci (including 10 novel loci isolated from <it>Chondrostoma nasus nasus, Chondrostoma toxostoma toxostoma </it>and <it>Leuciscus leuciscus</it>) for 503 individuals (440 purebred specimens and 63 hybrids) from 15 European cyprinid species. The level of genetic diversity was assessed in <it>Alburnus alburnus, Alburnoides bipunctatus, C. genei, C. n. nasus, C. soetta, C. t. toxostoma, L. idus, L. leuciscus, Pachychilon pictum, Rutilus rutilus, Squalius cephalus </it>and <it>Telestes souffia</it>. The applicability of the markers was also tested on <it>Abramis brama, Blicca bjoerkna </it>and <it>Scardinius erythrophtalmus </it>specimens. Overall, between 24 and 37 of these markers revealed polymorphic for the investigated species and 23 markers amplified for all the 15 European cyprinid species.</p> <p>Conclusions</p> <p>The developed set of markers demonstrated its performance in discriminating European cyprinid species. Furthermore, it allowed detecting and characterizing hybrid individuals. These microsatellites will therefore be useful to perform comparative evolutionary and population genetics studies dealing with European cyprinids, what is of particular interest in conservation issues and constitutes a tool of choice to conduct hybridization studies.</p

High sample throughput genotyping for estimating C-lineage introgression in the dark honeybee: an accurate and cost-effective SNP-based tool

The natural distribution of the honeybee (Apis mellifera L.) has been changed by humans in recent decades to such an extent that the formerly widest-spread European subspecies, Apis mellifera mellifera, is threatened by extinction through introgression from highly divergent commercial strains in large tracts of its range. Conservation efforts for A. m. mellifera are underway in multiple European countries requiring reliable and cost-efficient molecular tools to identify purebred colonies. Here, we developed four ancestry-informative SNP assays for high sample throughput genotyping using the iPLEX Mass Array system. Our customized assays were tested on DNA from individual and pooled, haploid and diploid honeybee samples extracted from different tissues using a diverse range of protocols. The assays had a high genotyping success rate and yielded accurate genotypes. Performance assessed against whole-genome data showed that individual assays behaved well, although the most accurate introgression estimates were obtained for the four assays combined (117 SNPs). The best compromise between accuracy and genotyping costs was achieved when combining two assays (62 SNPs). We provide a ready-to-use cost-effective tool for accurate molecular identification and estimation oinfo:eu-repo/semantics/publishedVersio

Drug Target Commons : A Community Effort to Build a Consensus Knowledge Base for Drug-Target Interactions

Knowledge of the full target space of bioactive substances, approved and investigational drugs as well as chemical probes, provides important insights into therapeutic potential and possible adverse effects. The existing compound-target bioactivity data resources are often incomparable due to non-standardized and heterogeneous assay types and variability in endpoint measurements. To extract higher value from the existing and future compound target-profiling data, we implemented an open-data web platform, named Drug Target Commons (DTC), which features tools for crowd-sourced compound-target bioactivity data annotation, standardization, curation, and intra-resource integration. We demonstrate the unique value of DTC with several examples related to both drug discovery and drug repurposing applications and invite researchers to join this community effort to increase the reuse and extension of compound bioactivity data.Peer reviewe

Variable Physical Drivers of Near-Surface Turbulence in a Regulated River

Inland waters, such as lakes, reservoirs and rivers, are important sources of climate forcing trace gases. A key parameter that regulates the gas exchange between water and the atmosphere is the gas transfer velocity, which itself is controlled by near-surface turbulence in the water. While in lakes and reservoirs, near-surface turbulence is mainly driven by atmospheric forcing, in shallow rivers and streams it is generated by bottom friction of gravity-forced flow. Large rivers represent a transition between these two cases. Near-surface turbulence has rarely been measured in rivers and the drivers of turbulence have not been quantified. We analyzed continuous measurements of flow velocity and quantified turbulence as the rate of dissipation of turbulent kinetic energy over the ice-free season in a large regulated river in Northern Finland. Measured dissipation rates agreed with predictions from bulk parameters, including mean flow velocity, wind speed, surface heat flux, and with a one-dimensional numerical turbulence model. Values ranged from  ~10-10m2s-3 to 10-5m2s-3. Atmospheric forcing or gravity was the dominant driver of near-surface turbulence for similar fraction of the time. Large variability in near-surface dissipation rate occurred at diel time scales, when the flow velocity was strongly affected by downstream dam operation. By combining scaling relations for boundary-layer turbulence at the river bed and at the air-water interface, we derived a simple model for estimating the relative contributions of wind speed and bottom friction of river flow as a function of depth.</p

Physical activity measured by accelerometry among adolescents participating in sports clubs and non-participating peers

The purpose of this descriptive cross-sectional study is to describe the amount and intensity of physical activity (PA) measured by accelerometry among adolescents participating in organized sports (SCP) and age-matched non-participating peers (NP). SCPs (332) and NPs (139) wore an accelerometer on the hip for seven days. PA was reported using the 1-min exponential moving average. The current moderate-to-vigorous physical activity (MVPA) recommendation of at least an average of 60 min of MVPA daily was reached by 85% of SCPs and 45% of NPs (p PA of Finnish adolescents participating in nine different organized sports and age-matched non-participating peers was measured by accelerometry for one week and the results are reported using the 1-min exponential moving average.Adolescents participating in many organized sports accumulated more PA than non-participants; this was observed in meeting the PA recommendations, total amount of PA at different intensities, and step count.The current PA recommendation of at least an average of 60 min of MVPA per day was reached by 85% of SCPs and 45% of non-participating peers. Vigorous physical activity at least three times per week was incorporated by 96% of SCPs and 81% of NPs. During training days, males participating in soccer, basketball, and cross-country skiing spent more time in MVPA than females participating in the same sports. During non-training days, the time spent in MVPA was similar between males and females participating in sports clubs.</ul